Knowledge of the metabolic factors controlling Ca 2 ions distribution across cell membranes is of vital importance in understanding the role of this metal ion in the regulation of glucose metabolism. It is proposed that glucogenic hormone action is in part mediated by the mobilization of subcellular Ca 2 ions. The objective of this proposal is to identify the cytoplasmic components (e.g. chemical messenger or metabolic state) required to couple hormone binding to the release of cellular Ca 2 ions in cAMP independent pathways in normal livers. Delineating the mechanisms of these control processes may aid in understanding glucose metabolism during diabetes mellitus and accelerated rates of glycolysis in certain tumors which exhibit abnormal mitochondrial Ca 2 ion metabolism. Rats have been chosen as the animal model because of the extensive literature concerning hormonal control of hepatic glucose metabolism, ion fluxes, and preparation of cellular and subcellular fractions. Ion flux measurements and reconstitution of biological activity will be used to investigate: a) hormone dependent changes in Ca 2 ion permeabilities; b) factors mediating hormone binding and mobilization of cellular Ca 2 ion, and c) the influence of altered steady state levels of Ca 2 ions on glycogenolysis and glucose metabolism.